PROJECT 2 - Abstract Nicotine has long been known to be the primary addictive substance in tobacco. The Food and Drug Administration (FDA) has the authority to regulate the nicotine levels (without eliminating it) on all tobacco products and is required to address this issue. Before implementing any policy, the FDA must make a thorough assessment of the likely impacts of the policy on the public?s health. While lowering nicotine levels might be expected to lead to declining smoking rates, such policies could generate unintended consequences that would undermine their effectiveness. Our proposed analysis will examine how nicotine regulation may impact the public?s health, including possible unintended consequences from compensation behaviors and the emergence of a black market. The results of this project will inform the FDA as it contemplates designing, evaluating and justifying a policy aimed at reducing nicotine in tobacco products to non-addictive levels. The Aims of the Project are: (1) to modify two existing US population-based dynamic smoking prevalence and mortality models to account for the effects of policies that reduce nicotine to non-addictive levels in all combusted tobacco products; (2) to model the number of new smokers, smoking prevalence trajectory, and smoking-related mortality in the US population from 2018-2100 in the absence of nicotine regulation; and (3) to conduct policy simulation exercises on the impact of nicotine regulations on smoking prevalence and associated mortality. We will focus on potential policy-related changes to smoking prevalence and overall mortality; however, other health outcomes may be incorporated as they become available from Project One. While the focus of the study will be on nicotine reduction, the models will be flexible enough to examine the effect of other FDA regulations to alter cigarette content, such as limits on particular toxic ingredients. This Project will focus on Impact Analysis (Aim 3) and Health Effects (Aims 2 and 3), with a secondary focus on Addiction (Aims 1 and 2), as described in RFA-OD-17-006.